بازداری واکنش و تکانشگری: مطالعه fMRI

Aggressive, suicidal and violent behaviour have been associated with impulsive personality and difficulty in inhibiting responses. We used functional magnetic resonance imaging (fMRI) of the whole brain to examine the neural correlates of response inhibition in 19 normal subjects as they performed a Go/NoGo task. Subjects completed Eysenck’s Impulsivity Scale, Barratt’s Impulsivity Scale (BIS) and behavioural impulsivity tasks. Associations between blood oxygen level dependent (BOLD) response, trait impulsivity, task performance and National Adult Reading Test (NART) IQ were investigated. Neural response during response inhibition was most prominent in the right lateral orbitofrontal cortex. Responses were also seen in superior temporal gyrus, medial orbitofrontal cortex, cingulate gyrus, and inferior parietal lobule, predominantly on the right side. Subjects with greater scores on impulsivity scales and who made more errors had greater activation of paralimbic areas during response inhibition, while less impulsive individuals and those with least errors activated higher order association areas. Exploratory factor analysis of orbital activations, personality measures and errors of commission did not reveal a unitary dimension of impulsivity. However, the strong association between posterior orbital activation and Eysenck’s impulsivity score on a single factor suggests that greater engagement of right orbitofrontal cortex was needed to maintain behavioural inhibition in impulsive individuals. Lower IQ was more important than impulsivity scores in determining errors of commission during the task. Neuroimaging of brain activity during the Go/NoGo task may be useful in understanding the functional neuroanatomy and associated neurochemistry of response inhibition. It may also allow study of the effects of physical and psychological interventions on response inhibition in clinical conditions such as antisocial personality disorder.

Impulsivity is a multidimensional concept that incorporates failure of response inhibition, rapid processing of information, novelty seeking, and inability to delay gratification (Barratt, 1985 and Barratt, 1994). Impulsivity is one of the defining characteristics of a number of psychiatric diagnoses, particularly borderline and antisocial personality disorders (Stein et al., 1993 and Stein et al., 1995). Poor impulse control correlates significantly with suicidal, violent and aggressive behaviour (Plutchik and Van Praag, 1989 and Plutchik and Van Praag, 1995) and is an increasingly important aspect of risk assessment in a variety of clinical situations, including assessment of dangerousness (Monahan et al., 2000). Most attempts to measure impulsivity rely on psychometric self-report trait measures. Some behavioural impulsivity tasks have been developed, measuring preference for a smaller more immediate reward over a delayed larger reward, and impaired motor inhibition, however, psychometric and behavioural impulsivity measures do not correlate well with each other (Barratt and Patton, 1983 and Barratt et al., 1997). Behavioural impulsivity tasks tend to have low test–retest reliability, apart from the Go/NoGo task, which has reasonable temporal stability (Kindlon, Mezzacappa, & Earls, 1995). Impulsivity is a feature of damage to the frontal lobe and an “acquired sociopathic” syndrome has been described following ventromedial frontal lobe lesions (Damasio, Tranel, & Damasio, 1990; Grafman et al., 1996; Paradiso et al., 1999 and Paradiso et al., 1999). This has lead to suggestions that impaired ventromedial frontal lobe function may contribute to poor impulse control in antisocial personality disorders (Damasio, 2000). In support of this notion a variety of neuropsychological deficits have been reported in antisocial populations (Morgan & Lilienfeld, 2000). Neuroimaging studies in this population report a reduction in prefrontal metabolism (Raine, Buchsbaum, & LaCasse, 1997), and reduced prefrontal grey matter volumes (Raine, Lencz, Bihrle, La Casse, & Colletti, 2000). Positron emission tomography (PET) (Kawashima et al., 1996; Krams et al., 1998 and Nobre et al., 1999) and functional Magnetic Resonance Imaging (fMRI) studies (Casey et al., 1997; Garavan, Ross, & Stein, 1999; Hager et al., 1998; Konishi, Nakajima, Uchida, Sekihara, & Miyashita, 1998) of response inhibition and processing novel stimuli suggest a role for the prefrontal cortex, especially the right lateral frontal cortex, and a network of associated regions in response inhibition. It is not clear to what extent these inhibition-related activations may depend on subjects’ impulsivity. Garavan, Ross, Murphy, Roche, & Stein (2002) have reported greater reliance on anterior cingulate cortex during Go/NoGo in subjects who are more absent-minded, using a cognitive measure that they have found to be correlated with Barrett’s Impulsivity Scale (BIS). The key novel aspect of the present study is the direct investigation of the relationship between trait impulsivity measures and blood oxygen level dependent (BOLD) response. We hypothesized that: (1) orbitofrontal cortex would be activated during response inhibition, (2) low scores on psychometric (trait) impulsivity measures would be associated with greater activation in orbitofrontal cortex during response inhibition, (3) low error-rates on the Go/NoGo response inhibition task would be associated with greater activation in the orbitofrontal cortex during response inhibition, (4) psychometric (trait) impulsivity scores would correlate positively with error-rate on response inhibition tasks.

Our findings support the hypothesis that the anterior lateral orbitofrontal cortex is activated during response inhibition. In addition, a network of higher order association and paralimbic areas was activated. While these regions are known to be anatomically connected and have been activated in this study, the challenge of elucidating the precise sequences of neural activity will require more sophisticated techniques, such as the use of brain evoked-potential measurement and event-related fMRI paradigms. We detected differences between the functional type of brain region activated during response inhibition and personality trait measures. More impulsive individuals activated paralimbic areas, particularly the right inferior frontal gyrus extending to posterior lateral orbitofrontal cortex and anterior insula, while less impulsive individuals activated higher order association areas when inhibiting a pre-potent response.